PDF(Pubmed)
Abstract：
UNASSIGNED: Understanding the heterogeneity of neuropsychiatric symptoms (NPSs) and associated brain abnormalities is essential for effective management and treatment of dementia.
UNASSIGNED: To identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes.
UNASSIGNED: Using data from the Open Access Series of Imaging Studies-3 (OASIS-3; recruitment began in 2005) and Alzheimer Disease Neuroimaging Initiative (ADNI; recruitment began in 2004) databases, this cross-sectional study analyzed resting-state functional magnetic resonance imaging (fMRI) scans, clinical assessments, and neuropsychological measures of participants aged 42 to 95 years. The fMRI data were processed from July 2022 to February 2024, with secondary analysis conducted from August 2022 to March 2024. Participants without medical conditions or medical contraindications for MRI were recruited.
UNASSIGNED: A multivariate sparse canonical correlation analysis was conducted to identify functional connectivity-informed NPS subsyndromes, including behavioral and anxiety subsyndromes. Subsequently, a clustering analysis was performed on obtained latent connectivity profiles to reveal neurophysiological subtypes, and differences in abnormal connectivity and phenotypic profiles between subtypes were examined.
UNASSIGNED: Among 1098 participants in OASIS-3, 177 individuals who had fMRI and at least 1 NPS at baseline were included (78 female [44.1%]; median [IQR] age, 72 [67-78] years) as a discovery dataset. There were 2 neuropsychiatric subsyndromes identified: behavioral (r = 0.22; P = .002; P for permutation = .007) and anxiety (r = 0.19; P = .01; P for permutation = .006) subsyndromes from connectivity NPS-associated latent features. The behavioral subsyndrome was characterized by connections predominantly involving the default mode (within-network contribution by summed correlation coefficients = 54) and somatomotor (within-network contribution = 58) networks and NPSs involving nighttime behavior disturbance (R = -0.29; P < .001), agitation (R = -0.28; P = .001), and apathy (R = -0.23; P = .007). The anxiety subsyndrome mainly consisted of connections involving the visual network (within-network contribution = 53) and anxiety-related NPSs (R = 0.36; P < .001). By clustering individuals along these 2 subsyndrome-associated connectivity latent features, 3 subtypes were found (subtype 1: 45 participants; subtype 2: 43 participants; subtype 3: 66 participants). Patients with dementia of subtype 3 exhibited similar brain connectivity and cognitive behavior patterns to those of healthy individuals. However, patients with dementia of subtypes 1 and 2 had different dysfunctional connectivity profiles involving the frontoparietal control network (FPC) and somatomotor network (the difference by summed z values was 230 within the SMN and 173 between the SMN and FPC for subtype 1 and 473 between the SMN and visual network for subtype 2) compared with those of healthy individuals. These dysfunctional connectivity patterns were associated with differences in baseline dementia severity (eg, the median [IQR] of the total score of NPSs was 2 [2-7] for subtype 3 vs 6 [3-8] for subtype 1; P = .04 and 5.5 [3-11] for subtype 2; P = .03) and longitudinal progression of cognitive impairment and behavioral dysfunction (eg, the overall interaction association between time and subtypes to orientation was F = 4.88; P = .008; using the time × subtype 3 interaction item as the reference level: β = 0.05; t = 2.6 for time × subtype 2; P = .01). These findings were further validated using a replication dataset of 193 participants (127 female [65.8%]; median [IQR] age, 74 [69-77] years) consisting of 154 newly released participants from OASIS-3 and 39 participants from ADNI.
UNASSIGNED: These findings may provide a novel framework to disentangle the neuropsychiatric and brain functional heterogeneity of dementia, offering a promising avenue to improve clinical management and facilitate the timely development of targeted interventions for patients with dementia.
UNASSIGNED: To identify dementia subtypes with distinct functional connectivity associated with neuropsychiatric subsyndromes.
UNASSIGNED: Using data from the Open Access Series of Imaging Studies-3 (OASIS-3; recruitment began in 2005) and Alzheimer Disease Neuroimaging Initiative (ADNI; recruitment began in 2004) databases, this cross-sectional study analyzed resting-state functional magnetic resonance imaging (fMRI) scans, clinical assessments, and neuropsychological measures of participants aged 42 to 95 years. The fMRI data were processed from July 2022 to February 2024, with secondary analysis conducted from August 2022 to March 2024. Participants without medical conditions or medical contraindications for MRI were recruited.
UNASSIGNED: A multivariate sparse canonical correlation analysis was conducted to identify functional connectivity-informed NPS subsyndromes, including behavioral and anxiety subsyndromes. Subsequently, a clustering analysis was performed on obtained latent connectivity profiles to reveal neurophysiological subtypes, and differences in abnormal connectivity and phenotypic profiles between subtypes were examined.
UNASSIGNED: Among 1098 participants in OASIS-3, 177 individuals who had fMRI and at least 1 NPS at baseline were included (78 female [44.1%]; median [IQR] age, 72 [67-78] years) as a discovery dataset. There were 2 neuropsychiatric subsyndromes identified: behavioral (r = 0.22; P = .002; P for permutation = .007) and anxiety (r = 0.19; P = .01; P for permutation = .006) subsyndromes from connectivity NPS-associated latent features. The behavioral subsyndrome was characterized by connections predominantly involving the default mode (within-network contribution by summed correlation coefficients = 54) and somatomotor (within-network contribution = 58) networks and NPSs involving nighttime behavior disturbance (R = -0.29; P < .001), agitation (R = -0.28; P = .001), and apathy (R = -0.23; P = .007). The anxiety subsyndrome mainly consisted of connections involving the visual network (within-network contribution = 53) and anxiety-related NPSs (R = 0.36; P < .001). By clustering individuals along these 2 subsyndrome-associated connectivity latent features, 3 subtypes were found (subtype 1: 45 participants; subtype 2: 43 participants; subtype 3: 66 participants). Patients with dementia of subtype 3 exhibited similar brain connectivity and cognitive behavior patterns to those of healthy individuals. However, patients with dementia of subtypes 1 and 2 had different dysfunctional connectivity profiles involving the frontoparietal control network (FPC) and somatomotor network (the difference by summed z values was 230 within the SMN and 173 between the SMN and FPC for subtype 1 and 473 between the SMN and visual network for subtype 2) compared with those of healthy individuals. These dysfunctional connectivity patterns were associated with differences in baseline dementia severity (eg, the median [IQR] of the total score of NPSs was 2 [2-7] for subtype 3 vs 6 [3-8] for subtype 1; P = .04 and 5.5 [3-11] for subtype 2; P = .03) and longitudinal progression of cognitive impairment and behavioral dysfunction (eg, the overall interaction association between time and subtypes to orientation was F = 4.88; P = .008; using the time × subtype 3 interaction item as the reference level: β = 0.05; t = 2.6 for time × subtype 2; P = .01). These findings were further validated using a replication dataset of 193 participants (127 female [65.8%]; median [IQR] age, 74 [69-77] years) consisting of 154 newly released participants from OASIS-3 and 39 participants from ADNI.
UNASSIGNED: These findings may provide a novel framework to disentangle the neuropsychiatric and brain functional heterogeneity of dementia, offering a promising avenue to improve clinical management and facilitate the timely development of targeted interventions for patients with dementia.
摘要：
■了解神经精神症状（NPSs）和相关大脑异常的异质性对于有效管理和治疗痴呆症至关重要。
■确定与神经精神亚综合征相关的具有不同功能连接的痴呆亚型。
使用开放获取系列成像研究-3（OASIS-3；招募始于2005年）和阿尔茨海默病神经成像计划（ADNI；招募始于2004年）数据库中的数据，这项横断面研究分析了静息状态功能磁共振成像（fMRI）扫描，临床评估，和42至95岁参与者的神经心理学测量。功能磁共振成像数据从2022年7月至2024年2月进行处理，从2022年8月至2024年3月进行二次分析。招募没有医疗条件或MRI医学禁忌症的参与者。
■进行了多变量稀疏典型相关分析，以识别功能连接信息的NPS子综合征，包括行为和焦虑子综合征。随后，对获得的潜在连接谱进行聚类分析，以揭示神经生理亚型，并检查了亚型之间异常连接和表型特征的差异。
■在OASIS-3的1098名参与者中，包括177名基线时具有fMRI和至少1NPS的个体（78名女性[44.1%]；中位[IQR]年龄，72[67-78]年)作为发现数据集。确定了2种神经精神亚综合征：行为（r=0.22;P=.002;P为排列=.007）和焦虑（r=0.19;P=.01;P为排列=.006）来自连通性NPS相关潜在特征的亚综合征。行为子综合征的特征是主要涉及默认模式（网络内贡献，相关系数=54）和躯体运动（网络内贡献=58）网络以及涉及夜间行为障碍的NPS（R=-0.29；P<.001），搅动（R=-0.28；P=.001），和冷漠（R=-0.23；P=0.007）。焦虑子综合征主要包括涉及视觉网络的连接（网络内贡献=53）和焦虑相关的NPS（R=0.36；P<.001）。通过沿着这两个亚综合征相关的连通性潜在特征聚类个体，发现3个亚型(亚型1:45名参与者;亚型2:43名参与者;亚型3:66名参与者)。3型痴呆症患者表现出与健康个体相似的大脑连通性和认知行为模式。然而,与健康个体相比,1亚型和2亚型痴呆患者在额叶控制网络(FPC)和躯体运动网络方面的功能失调性连接谱不同(对于1亚型,SMN和FPC的z值总和差异为230,对于2亚型,SMN和视觉网络的z值总和差异为173).这些功能失调的连接模式与基线痴呆严重程度的差异相关(例如，3型NPS总分的中位数[IQR]为2[2-7]，1型为6[3-8]；2型P=.04和5.5[3-11]；P=.03）和认知障碍和行为功能障碍的纵向进展（例如，时间和亚型与方向之间的总体相互作用关联为F=4.88；P=.008；使用时间×亚型3相互作用项作为参考水平：β=0.05；时间×亚型2的t=2.6；P=.01）。使用193名参与者的复制数据集（127名女性[65.8％];中位[IQR]年龄，74[69-77]年），由OASIS-3的154名新发布参与者和ADNI的39名参与者组成。
■这些发现可能提供一个新的框架来解开痴呆的神经精神和脑功能异质性，提供了一个有希望的途径，以改善临床管理，并促进及时开发针对痴呆症患者的有针对性的干预措施。
■确定与神经精神亚综合征相关的具有不同功能连接的痴呆亚型。
使用开放获取系列成像研究-3（OASIS-3；招募始于2005年）和阿尔茨海默病神经成像计划（ADNI；招募始于2004年）数据库中的数据，这项横断面研究分析了静息状态功能磁共振成像（fMRI）扫描，临床评估，和42至95岁参与者的神经心理学测量。功能磁共振成像数据从2022年7月至2024年2月进行处理，从2022年8月至2024年3月进行二次分析。招募没有医疗条件或MRI医学禁忌症的参与者。
■进行了多变量稀疏典型相关分析，以识别功能连接信息的NPS子综合征，包括行为和焦虑子综合征。随后，对获得的潜在连接谱进行聚类分析，以揭示神经生理亚型，并检查了亚型之间异常连接和表型特征的差异。
■在OASIS-3的1098名参与者中，包括177名基线时具有fMRI和至少1NPS的个体（78名女性[44.1%]；中位[IQR]年龄，72[67-78]年)作为发现数据集。确定了2种神经精神亚综合征：行为（r=0.22;P=.002;P为排列=.007）和焦虑（r=0.19;P=.01;P为排列=.006）来自连通性NPS相关潜在特征的亚综合征。行为子综合征的特征是主要涉及默认模式（网络内贡献，相关系数=54）和躯体运动（网络内贡献=58）网络以及涉及夜间行为障碍的NPS（R=-0.29；P<.001），搅动（R=-0.28；P=.001），和冷漠（R=-0.23；P=0.007）。焦虑子综合征主要包括涉及视觉网络的连接（网络内贡献=53）和焦虑相关的NPS（R=0.36；P<.001）。通过沿着这两个亚综合征相关的连通性潜在特征聚类个体，发现3个亚型(亚型1:45名参与者;亚型2:43名参与者;亚型3:66名参与者)。3型痴呆症患者表现出与健康个体相似的大脑连通性和认知行为模式。然而,与健康个体相比,1亚型和2亚型痴呆患者在额叶控制网络(FPC)和躯体运动网络方面的功能失调性连接谱不同(对于1亚型,SMN和FPC的z值总和差异为230,对于2亚型,SMN和视觉网络的z值总和差异为173).这些功能失调的连接模式与基线痴呆严重程度的差异相关(例如，3型NPS总分的中位数[IQR]为2[2-7]，1型为6[3-8]；2型P=.04和5.5[3-11]；P=.03）和认知障碍和行为功能障碍的纵向进展（例如，时间和亚型与方向之间的总体相互作用关联为F=4.88；P=.008；使用时间×亚型3相互作用项作为参考水平：β=0.05；时间×亚型2的t=2.6；P=.01）。使用193名参与者的复制数据集（127名女性[65.8％];中位[IQR]年龄，74[69-77]年），由OASIS-3的154名新发布参与者和ADNI的39名参与者组成。
■这些发现可能提供一个新的框架来解开痴呆的神经精神和脑功能异质性，提供了一个有希望的途径，以改善临床管理，并促进及时开发针对痴呆症患者的有针对性的干预措施。
